Research will be continued on three general lines: 1) The first is the regulation of somatomedin generation by liver. Our studies have indicated that insulin is a determinant of somatomedin release by the isolated rat liver. We plan to examine this question in man by administering insulin in a dose of 1-5 units/hour to hypopituitary subjects while maintaining blood sugar at 100mg%. This will be continued for 24 hours. Bioassayable and radioreceptor assayable somatomedin will be measured at 4 hour intervals. We will also study somatomedin generation in patients with growth hormone resistance of several types. We will continue our studies of somatomedin generation in vitro by studying the effect of addition of GH and insulin to isolated rat hepatocytes. We will collaborate in studies of hormonal effects on somatomedin generation by perfused rat liver. 2) We will isolate somatomedin from serum of rats bearing GH secreting tumors and compare this somatomedin with human somatomedin A and C prepared in other laboratories. Rat somatomedin will be used for radioreceptor assays in experiments of somatomedin generation by isolated hepatocytes and perfused rat livers. 3) We have obtained evidence that mid-term amniotic fluid contains a material which cross reacts strongly in the somatomedin C radioreceptor assay. We have observed that this material is smaller in size from the somatomedin in human plasma and cannot be easily dissociated. We plan to further characterize the physical properties and biologic activity of this material. It is possible that this may represent a unique fetal growth promoting substance which differs from somatomedin C. BIBLIOGRAPHIC REFERENCES: Daughaday, W.H., Phillips, L.S. and Herington, A.C.: Somatomedin generation by perfused liver. Advances in Metabolic Disorders 8:151,1975. Daughaday, W.H.: Somatomedin levels in human beings. Advances in Metabolic Disorders 8:159,1975.